Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

cGMP-dependent protein kinase type I (cGK I), a major constituent of the atrial natriuretic peptide (ANP)/nitric oxide/cGMP signal transduction pathway, phosphorylates the vasodilator-stimulated phosphoprotein (VASP), a member of the Ena/VASP family of proteins involved in regulation of the actin cytoskeleton. Here we demonstrate that stimulation of human umbilical vein endothelial cells (HUVECs) by both ANP and 8-(4-chlorophenylthio)guanosine 3':5'-monophosphate (8-pCPT-cGMP) activates transfected cGK I and causes detachment of VASP and its known binding partner (zyxin) from focal adhesions in >60% of cells after 30 min. The ANP effects, but not the 8-pCPT-cGMP effects, reversed after 3 h of treatment. In contrast, a catalytically inactive cGK Ibeta mutant (cGK Ibeta-K405A) was incapable of mediating these effects. VASP mutated (Ser/Thr to Ala) at all three of its established phosphorylation sites (vesicular stomatitis virus-tagged VASP-AAA mutant) was not phosphorylated by cGK I and was resistant to detaching from HUVEC focal adhesions in response to 8-pCPT-cGMP. Furthermore, activation of cGK I, but not of mutant cGK Ibeta-K405A, caused a 1.5-2-fold inhibition of HUVEC migration, a dynamic process highly dependent on focal adhesion formation and disassembly. These results indicate that cGK I phosphorylation of VASP results in loss of VASP and zyxin from focal adhesions, a response that could contribute to cGK alteration of cytoskeleton-regulated processes such as cell migration.
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PMID:Regulation of human endothelial cell focal adhesion sites and migration by cGMP-dependent protein kinase I. 1085 Dec 46

While a sensation of thirst causes severe distress for a certain proportion of cancer patients in the terminal stage, the factors contributing to this symptom have not been established. To clarify the association between sensation of thirst and medical factors, especially dehydration, a cross-sectional observational study was performed on terminally ill cancer patients receiving inpatient hospice care. On admission to a palliative care unit, 88 consecutive patients underwent blood sampling and were requested to rate the intensity of thirst on a visual analogue scale (VAS). Physicians prospectively evaluated factors that might potentially be contributing to the symptom. The mean VAS score for thirst was 5.0+/-2.8, and 18% of the patients complained of severe thirst with a VAS score of > or = 8. No significant correlations were observed between the VAS score for thirst and the values of total protein, blood urea nitrogen (BUN), creatinine, sodium, osmolality, hematocrit, atrial natriuretic peptide (ANP), and biochemical dehydration defined by the levels of BUN, creatinine, sodium and osmolality. On the other hand, dehydration defined by ANP level (< or = 15 pg/ml), hyperosmolality (> or = 300 mosmol/kg), gastrointestinal cancer, survival, performance status, oral intake, vomiting, and stomatitis were significantly associated with the severity of thirst. In addition, mouth breathing and opioids were determined to be a potential clinical cause of severe thirst when a retrospective chart review was carried out. In conclusion, sensation of thirst is a frequent symptom in terminally ill cancer patients and is associated with dehydration, hyperosmolality, poor general conditions, stomatitis, oral breathing, and opioids. Careful assessments and treatment of underlying causes is important to alleviate patients' distress.
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PMID:Determinants of the sensation of thirst in terminally ill cancer patients. 1140 Oct 96